Can we predict postinflammatory hyperpigmentation after laser treatment based on dermoscopic findings of solar lentigo?

Solar lentigo (SL) commonly occurs as hyperpigmented macules in areas exposed to ultraviolet radiation. It typically shows an increased number of melanocytes in the basal cell layer of the skin, with or without elongated rete ridges. This retrospective study aimed to evaluate the characteristic dermoscopic patterns, reflecting different histopathological features, which might be valuable in predicting the possibility of postinflammatory hyperpigmentation (PIH) occurring after laser treatment. In total, 88 Korean patients diagnosed with biopsy-proven SL (a total of 90 lesions were diagnosed) between January, 2016 and December, 2021 were included. Histopathological patterns were classified into six categories. Dermoscopic features were classified into six categories. Pseudonetwork pattern and rete ridge elongation showed a statistically significant negative correlation. This means that a flatter epidermis is likely to manifest as a pseudonetwork pattern. The erythema pattern showed a significant positive correlation with interface changes and inflammatory infiltration. Bluish-gray granules (peppering), a characteristic dermoscopic finding, showed significant positive correlations with interface changes, inflammatory infiltration, and dermal melanophages. Clinicians considering laser treatment for patients with SL should perform dermoscopic tests before treatment. The pseudonetwork relates to flattened epidermis and fewer Langerhans cells; thus, a lower remission of PIH after laser treatment might be expected. If bluish-gray granules or erythema are observed, inflammatory conditions are likely to be involved. In such cases, regression of the inflammatory response through drug therapy, such as topical corticosteroids, should be a priority option before laser treatment.

Let-7 miRNA and CDK4 siRNA co-encapsulated in Herceptin-conjugated liposome for breast cancer stem cells.

Recently, breast cancer stem cells (BCSCs) have rapidly emerged as a novel target for the therapy of breast cancer as they play critical roles in tumor growth, maintenance, metastasis, and recurrence. Let-7 miRNA is known to be downregulated in a variety of cancers, especially BCSCs, whereas CDK4 being overexpressed in human epidermal growth factor receptor 2 (HER-2) overexpressing tumor cells. In this study, let-7 miRNA and CDK4-specific siRNA were chosen as therapeutic agents and co-encapsulated in Herceptin-conjugated cationic liposomes for breast cancer therapy. Particle size, zeta potential, and encapsulation efficacy of mi/siRNA-loaded PEGylated liposome conjugated with Herceptin (Her-PEG-Lipo-mi/siRNA) were 176 nm, 28.1 mV, and 99.7% ± 0.1%, respectively. Enhanced cellular uptake (86%) was observed by fluorescence microscopy when SK-BR-3 cells were treated with Her-PEG-Lipo-mi/siRNA. Also, the increased amount of let-7a mRNA and decreased amount of cellular CDK4 mRNA were observed by qRT-PCR when SK-BR-3 cells were treated with Her-PEG-Lipo-mi/siRNA, which was even more so when SK-BR-3 stem cells were used (197 vs 768 times increase for let-7a, 62% vs 68% decrease for CDK4). Growth inhibition (65%) and migration arrest (0.5%) of the cells were achieved by the treatment of the cells with Her-PEG-Lipo-mi/siRNA, but not with mi/siRNA complex or other formulations. In conclusion, an efficient liposomal delivery system for the combination of miRNA and siRNA to target the BCSCs was developed and could be used as an efficacious therapeutic modality for breast cancer.

Evaluation for Skin Cancer and Precancer in Patients With Vitiligo Treated With Long-term Narrowband UV-B Phototherapy.

Importance: Narrowband UV-B (NBUVB) phototherapy has been the mainstay in the treatment of vitiligo, but its long-term safety in terms of photocarcinogenesis has not been established. Objectives: To investigate the risks of skin cancer and precancerous lesions among patients with vitiligo undergoing NBUVB phototherapy, based on the number of NBUVB phototherapy sessions. Design, Setting, and Participants: This nationwide population-based retrospective cohort study enrolled 60 321 patients with vitiligo 20 years or older between January 1, 2007, and December 31, 2017. Patients and outcomes were identified through nationwide cohort data from the Korean national health insurance claims database, and frequency matching by age and sex was performed. Exposures: The number of phototherapy sessions each patient received between 2008 and 2017. Patients were classified into 5 groups according to the number of phototherapy sessions (0 sessions, 20 105 patients; 1-49 sessions, 20 106 patients; 50-99 sessions, 9702 patients; 100-199 sessions, 6226 patients; and ≥200 sessions, 4182 patients). We also identifed patients who underwent at least 500 phototherapy sessions (717 patients). Main Outcomes and Measures: Primary outcomes were the development of actinic keratosis, Bowen disease, nonmelanoma skin cancer, or melanoma after enrollment. Results: Among the 60 321 patients with vitiligo in this study (33 617 women; mean [SD] age, 50.2 [14.9] years), the risks of Bowen disease (<50 sessions of phototherapy: hazard ratio [HR], 0.289 [95% CI, 0.060-1.392]; 50-99 sessions: HR, 0.603 [95% CI, 0.125-2.904]; 100-199 sessions: HR, 1.273 [95% CI, 0.329-4.924]; ≥200 sessions: HR, 1.021 [95% CI, 0.212-4.919]), nonmelanoma skin cancer (<50 sessions: HR, 0.914 [95% CI, 0.533-1.567]; 50-99 sessions: HR, 0.765 [95% CI, 0.372-1.576]; 100-199 sessions: HR, 0.960 [95% CI, 0.453-2.034]; ≥200 sessions: HR, 0.905 [95% CI, 0.395-2.073]), and melanoma (<50 sessions: HR, 0.660 [95% CI, 0.286-1.526]; 50-99 sessions: HR, 0.907 [95% CI, 0.348-2.362]; 100-199 sessions: HR, 0.648 [95% CI, 0.186-2.255]; ≥200 sessions: HR, 0.539 [95% CI, 0.122-2.374]) did not increase after phototherapy. The risk of actinic keratosis increased significantly for those who had undergone 200 or more NBUVB phototherapy sessions (HR, 2.269 [95% CI, 1.530-3.365]). A total of 717 patients with vitiligo underwent at least 500 sessions of NBUVB phototherapy; their risks of nonmelanoma skin cancer and melanoma were no greater than those of the patients who did not undergo NBUVB phototherapy (nonmelanoma skin cancer: HR, 0.563 [95% CI, 0.076-4.142]; melanoma: HR, not applicable). Conclusions and Relevance: Our results suggest that long-term NBUVB phototherapy is not associated with an increased risk of skin cancer in patients with vitiligo and that NBUVB phototherapy may be considered a safe treatment.

The 308-nm excimer laser treatment does not increase the risk of skin cancer in patients with vitiligo: A population-based retrospective cohort study.

A 308-nm excimer laser (EL) has been widely used to treat patients with localized vitiligo. However, data are rare on the influence of EL treatment on the risks of skin cancer. To evaluate the skin cancer risks after long-term EL treatment, we performed a nationwide population-based retrospective cohort study using the Korean National Health Insurance Claims Database. A total of 5,052 patients with vitiligo were classified into three groups according to the EL treatment sessions between 2009 and 2016: no, 50-99, and 100 or more EL treatments after 2-year washout period (2007 and 2008). Using multivariable Cox proportional hazard models, we found that the risks of actinic keratosis, non-melanoma skin cancers, and melanoma did not significantly differ among the groups, respectively. In conclusion, EL treatment would not increase the risks of premalignant skin lesions and skin cancers in patients with vitiligo. Based on our results, EL is likely to be a safe treatment option for patients with localized vitiligo.

Clinical Features and Awareness of Hand Eczema in Korea.

BACKGROUND: Hand eczema is one of the most common skin disorders and negatively affects quality of life. However, a large-scale multicenter study investigating the clinical features of patients with hand eczema has not yet been conducted in Korea. OBJECTIVE: To identify the prevalence of various hand diseases, which is defined as all cutaneous disease occurring in hands, and to investigate the clinical features of patients with hand eczema and the awareness about hand eczema in the general population and to compare the prevalence of hand eczema between health care providers and non-health care providers. METHODS: To estimate the prevalence of hand diseases, we analyzed the medical records of patients from 24 medical centers. Patients were assessed by online and offline questionnaires. A 1,000 from general population and 913 hand eczema patients answered the questionnaire, for a total of 1,913 subjects. RESULTS: The most common hand disease was irritant contact dermatitis. In an online survey, the lifetime prevalence of hand eczema was 31.2%. Hand eczema was more likely to occur in females (66.0%) and younger (20~39 years, 53.9%). Health care providers and housewives were the occupations most frequently associated with hand eczema. Winter (33.6%) was the most common season which people experienced aggravation. The 63.0% and 67.0% answered that hand eczema hinders their personal relationship and negatively affects daily living activities, respectively. CONCLUSION: Hand eczema is a very common disease and hinders the quality of life. The appropriate identification of hand eczema is necessary to implement effective and efficient treatment.

A case of pulmonary sarcoidosis with endobronchial nodular involvement.

Sarcoidosis is a multisystemic disorder of unknown cause that is characterized pathologically by noncaseating granulomas. Diagnosis is based on the exclusion of other infectious, interstitial, and neoplastic diseases and on the typical pathology. Although the lungs and mediastinal lymph nodes are almost involved, endobronchial nodular lesions of sarcoidosis with lung involvements are rare. We report a case of sarcoidosis with lung involvements and endobronchial nodules as confirmed by bronchial biopsy.

Predictive factors of relapse in adult with Henoch-Schönlein purpura.

Henoch-Schönlein purpura (HSP) is an IgA-mediated small vessel vasculitis with a predominant cutaneous involvement. We assessed adult patients with HSP to identify the clinical and histopathological features and evaluate predictive factors of relapse. We reviewed the records of 29 adult patients with HSP who presented at our department between 2002 and 2009. Adult HSP was confirmed by skin biopsy showing leukocytoclastic vasculitis and direct immunofluorescence showing IgA deposit. Among the 29 patients (15 men, 14 women; mean age 36.2 years old), renal involvement was initially found in 22 patients (75.9%). They were divided into 2 groups according to the presence or absence of relapse. We compared clinical and histopathologic differences between 15 patients with relapse and 14 patients without relapse. By univariate analysis, older age at onset, persistent rash, abdominal pain, hematuria, and underlying disease at the onset of HSP are significantly related to relapse. Among the histopathological variables, severity of leukocytoclasis and absence of IgM deposit on the vessel walls are significantly associated to relapsing disease (P < 0.05). Our results are significant, because, they may help to understand the predictive factors related to relapses of HSP in adults. Further studies are necessary to identify whether more aggressive treatment in adults with HSP with these predictive factors can prevent relapse and severe renal sequelae.

Skin rejuvenating effects of chemical peeling: a study in photoaged hairless mice.

BACKGROUND: Chemical peeling is a dermatologic treatment for skin aging. However, the mechanism by which the chemical peel achieves its results is not clear. We investigated the effects of chemical peeling and the mechanism of wrinkle reduction in photoaged hairless mice skin. METHODS: After inducing photoaged skin in hairless mice by repetitive ultraviolet-B irradiation applied over 14 weeks, we applied trichloroacetic acid (TCA) 30%, TCA 50%, and phenol on areas of the same size on the backs of the mice. Punch biopsies were obtained 7, 14, 28, and 60 days after the procedure for histologic and immunohistochemical analyses. RESULTS: Histologic examination showed an increase in dermal thickness, collagen fibers, and elastic fibers in the dermis of intervention groups compared with control groups. These increases were maintained significantly for 60 days. CONCLUSIONS: This study demonstrates that chemical peeling reduces wrinkles and regenerates skin by increasing dermal thickness and the amount of collagen and elastic fibers in photoaged skin.

Photodistributed telangiectasia induced by amlodipine.

Calcium channel blockers are widely used antihypertensive drugs, which are uncommonly associated with cutaneous reactions, such as pruritus, urticaria, or alopecia. Photosensitivity presenting with telangiectasia has rarely been described. We present here a case of photodistributed telangiectasia induced clinically by amlodipine and histologically by enlarged capillaries in the upper dermis without signs of vasculitis.

A multicenter study on extramammary Paget's disease in Korea.

BACKGROUND: There has been little research on extramammary Paget's disease (EMPD) conducted in Asia. METHODS: The aim of this multicenter study was to investigate the clinicopathological features, biological behavior, and treatment of EMPD in 194 Korean patients over a five-year period. RESULTS: As expected, this disease exhibited a male dominance (3.9:1) pattern. To distinguish the true association of malignancy with EMPD from coincidental occurrence of malignancy, we modified Chanda's guidelines. This analysis determined that there was an accompanying malignancy in 26 patients (14.4%), which included stomach (six cases), rectum (three cases), and colon (three cases) malignancies. With regard to treatment, 112 patients (58%) underwent conventional excisions, and 22 (11.4%) had Mohs surgery. Follow-up data for periods of 3-180 months were available for 147 patients; these data indicated that 42 patients (28.6%) experienced local recurrences. Patients who underwent Mohs micrographic surgery experienced a lower rate of recurrence (12.5%) than patients who underwent conventional excision (33.3%). CONCLUSIONS: In summary, this Korean population-based study demonstrated that the clinical features of EMPD, such as gender predominance, are consistent with reports from other Asian population-based studies. However, this study additionally demonstrated that the rate of association with malignancy in the Korean population (14.4%) was higher than that observed in other Asian studies.

A stimulatory effect of Cassia occidentalis on melanoblast differentiation and migration.

In vitiligo, the active melanocytes in the epidermis are totally missing, whereas melanoblast cells in the outer root sheath of hair follicles are not affected. In an attempt to find potent repigmenting agents for vitiligo therapy, pod extracts of Cassia occidentalis was found to be effective in inducing differentiation and migration of mouse melanoblast cell line. Methanolic extract redissolved in DMSO at 12.5 µg/ml was found to cause 3.5- to 3.8-fold melanin induction in melb-a melanoblast cells after 4 days in treatment medium. In addition it induced the tyrosinase activity and altered melb-a cell morphology. Transwell migration assay showed the potential of this herbal candidate to induce direct migration of treated cells. To the best of our knowledge, this is the first report investigating the effect of Cassia occidentalis on the differentiation and migration of melanoblast cells. The findings of present study are significant in designing preclinical and clinical studies on the efficacy of C. occidentalis as a stimulant for skin repigmentation in vitiligo.

Development of a protein chip to measure PKCß activity.

Phosphorylation of proteins by kinases plays an important role in regulating cellular processes including melanin production in the skin cells. Protein kinase C ß (PKCß) is known to be involved in phosphorylating tyrosinase, the key enzyme of melanin production, regulating the skin pigmentation process. In melanogenesis, PKCß activates the tyrosinase by phosphorylation of its two serine residues. In this study, phosphorylation activity by PKCß was monitored on a protein chip for the screening of depigmenting agents. As a tyrosinase mimic, 11 or 30 amino acids of the C-terminal of tyrosinase was fused with maltose-binding protein (MBP). After immobilizing the MBP-fused PKCß substrate peptide on epoxy-treated slide surface, PKCß reaction mix was applied over the immobilized MBP-fused PKCß substrate peptide. Phosphorylation was detected with anti-phosphoSer/Thr antibodies, followed by fluorescence-labeled second antibodies. Phosphorylation of MBP-30aa was observed on a protein chip, and this phosphorylation was inhibited by the PKC inhibitor (GF109203X). These results indicate the potential of PKCß protein chip as a high-throughput screening tool in the screening of depigmenting agents.

A case of cicatricial alopecia associated with erlotinib.

Erlotinib is a small-molecule tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR). Erlotinib has been used primarily to treat non-small cell lung cancer. In addition to its role in tumor cells, EGFR is also an important regulator of growth and differentiation in the skin and hair. Therefore, EGFR-TKIs have been associated with a number of cutaneous side effects including follicular acneiform eruptions, cutaneous xerosis, chronic paronychia, desquamation, seborrheic dermatitis, and hair texture changes. Herein, we report a rare case of a 61-year-old woman who was treated with erlotinib and experienced cicatricial alopecia.

Acral angioosteoma cutis.

Acral angioosteoma cutis is a benign lesion of unknown pathogenesis and is a newly described, distinct entity from other cutaneous lesions. It is clinically characterized by an exophytic lesion resembling pyogenic granuloma on the acral skin, combined with histologic findings of multiple tiny spicules composed of woven bone between well-formed capillaries proliferating in the superficial dermis. Here, we present a case of acral angioosteoma cutis on the left third toe of a 58-year-old woman, which was successfully treated by excision.

A case of neutrophilic dermatosis of the dorsal hands with concomitant involvement of the lips.

Neutrophilic dermatosis of the dorsal hands (NDDH) is a localized, pustular variant of acute febrile neutrophilic dermatosis (Sweet syndrome). The lesions of NDDH clinically resemble those of Sweet syndrome (SS), but they differ from classic SS according to their locations (NDDH is predominantly restricted to the dorsal hands) and the smaller number of accompanying systemic symptoms. The histology of the NDDH lesion shows a dense dermal neutrophilic infiltration. The lesions rapidly resolve after systemic corticosteroid and/or dapsone therapy. We herein report on a case of neutrophilic dermatosis of the dorsal hands in a 34-year-old woman. The patient also had skin changes with erythematous plaque on the right lips.

Water-retentive and anti-inflammatory properties of organic and inorganic substances from Korean sea mud.

Sea mud has been popularly used as an effective base in cosmetic preparations although its biologically-active materials and mechanisms on skin have not yet been fully determined. We isolated humic substances as the major organic substance of the sea mud from a tidal flat in Korea, and investigated their water-retentive properties. Among the three isolated humic substances, humic acid (HA) showed the highest water retentive property (approximately 50 % mass increase from water uptake). Based on the observations that mud pack therapy has been traditionally used to soothe UV-irradiated skin, we examined the antiinflammatory property of the sea mud on UVB-irradiated human keratinocytes (HaCaT cells) by measuring PGE2 levels produced by keratinocytes in the presence of either the total water or methanol extracts of the mud. The water extract showed higher inhibition of PGE2 production from HaCaT cells (30% inhibition) than the methanol extract at 200 ppm (microg/g). We further fractionated the water extract to determine the major components responsible for its anti-inflammatory effect. It was found that the minerals in the mud inhibited PGE2 production by 83 % at 200 ppm, which is comparable with the inhibitory effect of 1 microM indomethacin. No mud extract showed cytotoxicity at the tested concentrations. The mineral compositions of the mineral extract were determined by ICP-MS, revealing that the sea mud consisted of more than 19 different mineral components, rich in Na+, Mg2+, and Zn2+. These results imply that the anti-inflammatory effect of the sea mud is largely due to the minerals in the mud. Our research suggests the potential use of the organic and inorganic substances from the sea mud in various skin products as safe biological substances for skin protective purposes.

Visualization of the melanosome transfer-inhibition in a mouse epidermal cell co-culture model.

Transfer of melanin-containing melanosomes from melanocytes to neighboring keratinocytes results in skin pigmentation. To provide a more practical method of visualizing melanosomes in melanocytes as well as in keratinocytes, we attempted to use murine cell lines instead of human primary cells. We generated various fluorescent fusion proteins of tyrosinase, a melanin synthesis enzyme located in the melanosome, by using green fluorescent protein and red fluorescent protein. The intracellular localization of tyrosinase was then examined by fluorescence and confocal microscopy. Co-culture of murine melanocytes and keratinocytes was optimized and melanosome transfer was either stimulated with alphaMSH or partially inhibited by niacinamide. To the best of our knowledge, this is the first study showing that a murine co-culture model, in addition to human primary cell co-culture, can be a good tool for depigmenting agent screening by monitoring melanosome transfer.